PROJECT SUMMARY NMR spectroscopy is a highly versatile and powerful biophysics method suitable for structural and chemical analysis of macromolecules as well as small-molecule chemical compounds. Funding is sought to upgrade our Bruker 600 MHz NMR spectrometer system with state-of-the-art AVANCE NEO console system at the Icahn School of Medicine at Mount Sinai. The proposed equipment upgrade consists of three main components: (1) a high performance AVANCE NEO console; (2) a high-sensitivity X-nuclei-optimized double resonance broad banded probe (SmartProbe); and (3) an automatic NMR sample changer. This NMR system is available to all investigators at the Icahn School of Medicine at Mount Sinai, and the instrument upgrade will greatly enhance its ongoing support for NIH-funded research projects by major users that study structure-function and molecular mechanisms of macromolecules as well as development of novel small-molecule chemical compounds as research probes and drug molecules for a wide range of proteins and pathways important in biology and human diseases.